This invention pertains to disease diagnosis, prediction and treatment and, more particularly, to diagnosis, prediction and treatment of asthma, rhinitis and other inflammatory conditions associated with eosinophil accumulation in respiratory and other tissues.
Asthma is a respiratory ailment characterized by airway obstruction, inflammation and/or hyper-responsiveness. According to a 1994 survey by the U.S. Department of Health and Human Services, over 12 million Americans suffer from asthma, almost 5 million of them under the age 18. Long-term medications include corticosteroid, beta-agonists and leukotriene modifiers. For quick relief, anticholinergics, corticosteroids, and/or beta-agonists may be applied. Adverse side effects of these treatments include cough, dysphonia, candidiasis (corticosteroids), tachycardia, muscle tremor, hypokalemia, hyperglycemia (beta-agonists), liver impairment (leukotriene modifiers), drying of mouth and respiratory secretions (anticholinergics).
The standard of care for asthma dictates that treatment with the foregoing medications be a guided by disease severity of the symptoms. Since the nature of asthma is to have exacerbations and remissions, this approach undertreats patients with the potential to develop significant airway inflammation, but who at the time of pulmonary function testing are in a physiological remission. In addition, this approach can result in application of medications of greater toxicity then truly required for the condition.
One characteristic of inflammatory reactions, such as asthma and rhinitis, is the accumulation of eosinophils in the mucosal lining of the affected organs. Recruitment of eosinophils is thought to be mediated by a class of proteins known as chemokines and, particularly, by the protein eotaxin. That ligand is understood to have a high affinity for so-called CC-CKR3 receptors, which are found in large numbers on the surfaces of eosinophils.
In view of the foregoing, an object of this invention use to provide improved compounds and methods for prediction, diagnosis and treatment of disease and, more particularly, improved compounds and methods for prediction, diagnosis and treatment of asthma, rhinitis and other inflammatory conditions of respiratory and other tissues.
A further object of the invention is to provide such improved compounds and methods as permit control of such inflammatory conditions without undue risk of under- or overtreatment.
Yet another object of the invention is to provide such improved compounds and methods as permit prediction, diagnosis and treatment of such inflammatory conditions in a cost effective manner.